A Missense Mutation rs781536408 (c.2395G>A) of TYK2 Affects Splicing and Causes Skipping of Exon18 in vivo

TYK2 variants can impact disease onset or progression. In our previous study, we identified abnormal splicing that happened near rs781536408 in the TYK2 gene. The purpose of this research was to examine the effect of the mutation on alternative splicing in vivo and in vitro. Whole exome sequencing was performed to identify the mutations followed by bidirectional Sanger sequencing. Then the minigene analysis was carried out based on HeLa and HEK293T cell lines. The results showed that rs781536408 (c.2395G>A, p.G799R) was homozygous in the patient, but heterozygous in parents. PCR amplification confirmed the abnormal splicing in the somatic cells of the patients, but not in the parents. Sanger sequencing results showed that there was a skipping of exon18 near the mutation. For minigene analysis, there was no difference between the wild-type and the mutant type in the two minigene construction strategies, indicating that mutation c.2395G>A had no effect on splicing in vitro. Combining the results of in vivo, we speculated that the effect of the mutation on splicing was not absolute, but rather in degree

The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation

<p>Abstract</p> <p>Background</p> <p>This paper investigates the effects of a new radiosensitizer, doranidazole, and enhancing irradiation on colorectal cancer cells.</p> <p>Methods</p> <p>The radiosensitizing effect of doranidazole was determined using colony formation and propidium iodide (PI) assays to measure cell growth inhibition and the cell killing effect of human colorectal cancer cell lines exposed to high doses of γ-ray irradiation under hypoxic conditions <it>in vitro</it>. Fluorescence staining and cell migration assays were also used to assess the radiosensitizing effect.</p> <p>Results</p> <p>Cell proliferation evaluated by clonogenic survival curves was significantly inhibited by 5 mmol/L doranidazole, particularly at doses ranging from 10 to 30 Gy of irradiation. The radiosensitizing effect of doranidazole on colorectal cancer cells occurs in a time- and dose-dependent manner. Doranidazole also inhibited the mobility of cell invasion and migration.</p> <p>Conclusion</p> <p>Doranidazole can enhance the killing effect and the cell growth inhibition of colorectal cancer after high-dose irradiation in a time and dose-dependent manner.</p

Cell growth and cell death of Colo 201 exposed to Doranidazole for 4 days

<p><b>Copyright information:</b></p><p>Taken from "The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation"</p><p>http://www.biomedcentral.com/1471-2407/7/188</p><p>BMC Cancer 2007;7():188-188.</p><p>Published online 6 Oct 2007</p><p>PMCID:PMC2082041.</p><p></p

Detection of UGT1A1*28 Polymorphism Using Fragment Analysis

Background and objective Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism. Methods A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method. Results Comparing with Sanger sequencing, precision and accuracy of the fragment analysis method were 100%. Of the 286 patients, 236 (82.5% harbored TA6/6 genotype, 48 (16.8%) TA 6/7 genotype and 2 (0.7%) TA7/7 genotype. Conclusion Our data suggest hat the fragment analysis method is robust for detecting UGT1A1*28 polymorphism in clinical practice. It’s simple, time-saving, and easy-to-carry

Cell survival curve of Colo 201 after different doses of irradiation under hypoxia in the presence or absence of 5 mmol/L Doranidazole

<p><b>Copyright information:</b></p><p>Taken from "The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation"</p><p>http://www.biomedcentral.com/1471-2407/7/188</p><p>BMC Cancer 2007;7():188-188.</p><p>Published online 6 Oct 2007</p><p>PMCID:PMC2082041.</p><p></p

Identification of Peanut <i>Aux/IAA</i> Genes and Functional Prediction during Seed Development and Maturation

Auxin-responsive genes AUX/IAA are important during plant growth and development, but there are few relevant reports in peanut. In this study, 44 AhIAA genes were identified from cultivated peanut, of which 31 genes were expressed in seed at varying degrees. AhIAA-3A, AhIAA-16A and AhIAA-15B were up-regulated, while AhIAA-11A, AhIAA-5B and AhIAA-14B were down-regulated with seed development and maturation. The expression patterns of seven genes, AhIAA-1A, AhIAA-4A, AhIAA-10A, AhIAA-20A, AhIAA-1B, AhIAA-4B and AhIAA-19B, were consistent with the change trend of auxin, and expression in late-maturing variety LM was significantly higher than that in early-maturing EM. Furthermore, allelic polymorphism analysis of AhIAA-1A and AhIAA-1B, which were specifically expressed in seeds, showed that three SNP loci in 3′UTR of AhIAA-1A could effectively distinguish the EM- and LM- type germplasm, providing a basis for breeding markers development. Our results offered a comprehensive understanding of Aux/IAA genes in peanut and provided valuable clues for further investigation of the auxin signal transduction pathway and auxin regulation mechanism in peanut